Resveratrol, a phytoalexin (3, 4', 5, trihydroxystilbene) present in some red wines, has been reported to inhibit copper-mediated low-density lipoprotein (LDL) oxidation. In this study, we examined the efficiency of this compound in inhibiting metal ion-dependent and independent peroxidation of porcine LDL. At 0.5, 1, or 1.5 microM, transresveratrol prolonged the lag time preceding the onset of conjugated diene formation in a dose-dependent manner, with a slope of the propagation phase 5-fold greater in the presence of Cu SO4 (5 microM) than in the presence of the free radical generator, AAPH [2, 2'-azobis (2-amidinopropane) dihydrochloride] (1 mM). At 1 microM, transresveratrol prolonged the lag time 3.4- and 1.4-fold in the presence of copper and AAPH, respectively. Isomerisation into cisresveratrol significantly lowered the chelating capacity, but did not alter the free radical scavenging capacity. As compared to flavonoids and trolox, transresveratrol showed a much higher ability to prolong the lag time in copper, but not in AAPH-catalyzed oxidation. The kinetics of generation of degradative products in the presence of copper confirmed the strongest protective effects of transresveratrol, because the formation of thiobarbituric acid reactive substances and hydroperoxides was almost completely inhibited at 200 min. By contrast, transresveratrol was less potent than flavonoids (but more than trolox) as a scavenger of free radicals. Our data show that, like flavonoids, resveratrol protects LDL against peroxidative degradation by both chelating and free radical scavenging mechanisms. However, transresveratrol, which is by far the most potent chelator of copper, does not chelate iron. It might contribute to the protective effects of wine polyphenols by removing copper from LDL particles and arterial tissue and, thereby, delaying the consumption of flavonoids and endogenous antioxidants.